Guidelines

International Journal of STD & AIDS

2020, Vol. 31(1) 4–15
2018 UK national guideline for the ! The Author(s) 2019
Article reuse guidelines:
management of infection with sagepub.com/journals-permissions
DOI: 10.1177/0956462419886775
Neisseria gonorrhoeae journals.sagepub.com/home/std

Helen Fifer1 , John Saunders2, Suneeta Soni3, S Tariq Sadiq4

and Mark FitzGerald5

Changes since 2011 guideline RIGOUR OF DEVELOPMENT

• First line empirical treatment is now monotherapy This guideline was produced according to specifications
with ceftriaxone 1 g intramuscularly set out in the CEG’s 2015 document ‘Framework for
• If antimicrobial susceptibility test results from all guideline development and assessment’ outlined at
sites of infection are available prior to treatment https://www.bashh.org/bashh-groups/clinical-effective
and the isolate is sensitive to ciprofloxacin, then ness-group/ and has been updated by reviewing the
this should be used for treatment in preference to previous gonorrhoea guideline (2011) and medical lit-
ceftriaxone erature since its publication. A MEDLINE search of
• Inclusion of testing recommendations in people fol- published articles in English language for the years
lowing genital reconstructive surgery 2009–18 was done using the subject headings ‘gonor-
• Recommendations for extra-genital testing in those rhoea’ OR ‘gonorrhea’ OR ‘Neisseria gonorrhoeae’
with suspected or confirmed antimicrobial resistance AND ‘therapy’ OR ‘treatment’ OR ‘therapeutics’ OR
• Epidemiological treatment is recommended only ‘resistance’ OR ‘anti-bacterial agents’ OR ‘antibiotics’
for those presenting within 14 days of exposure. OR ‘failure’ OR ‘toxicity’. All entries in the English
For those presenting after 14 days of exposure we language or with abstracts in English were viewed
recommend treatment based on the results of because of the paucity of ‘clinical trials’ or ‘reviews’.
testing The Cochrane Database of Systematic Reviews,
Database of Abstracts of Reviews of Effectiveness
SCOPE AND PURPOSE and Cochrane Controlled Trials Register were reviewed
using the textword ‘gonorrhoea’ and all entries were
This guideline offers recommendations for the diagnos-
considered. Abstracts from meetings in the relevant
tic tests, treatment regimens and health promotion
period were hand-searched and considered. Priority
principles needed for the effective management of gon-
was given to randomized controlled trials and
orrhoea in people aged 16 years and older. For indi-
viduals under the age of 16 years please see the British
Association for Sexual Health and HIV (BASHH)
guideline on STI and Related Conditions in Children 1
Consultant Microbiologist, National Infection Service, Public Health
and Young People. The guidelines are primarily aimed England
2
at level 3 sexual health services within the United Consultant in Sexual Health, National Infection Service, Public Health
England and Central and North West London NHS Foundation Trust
Kingdom (UK) although the principles of the recom- 3
Consultant in Sexual Health, Brighton & Sussex University Hospitals
mendations could be adopted at all levels. NHS Trust
4
Professor of Molecular Medicine, Institute for Infection and Immunity, St
George’s, University of London
EDITORIAL INDEPENDENCE 5
Consultant in Sexual Health, Clinical Effectiveness Group, BASHH
This guideline was commissioned and edited by the
Corresponding author:
Clinical Effectiveness Group (CEG) of BASHH, Helen Fifer, Public Health England, 61 Colindale Avenue, London, NW9
which provided funding for the literature search. No 5EQ, UK.
other funding was obtained. Email: [email protected]
Fifer et al. 5

systematic review evidence. Recommendations were complain of testicular and epididymal pain with ten-
made and graded on the basis of best available evi- derness and swelling present on examination.
dence. There is a scarcity of high quality evidence to
guide treatment recommendations and therefore, a Female urethral infection
meeting was held in June 2018 to discuss and resolve
Urethral infection may present with dysuria without
differences in opinion surrounding treatment recom-
urinary frequency.
mendations. This was attended by representatives
from the guideline writing group, the CEG, the
Gonococcal Resistance to Antimicrobials Surveillance
Endocervical infection
Programme (GRASP) Steering Group and the BASHH The most common symptom, occurring in about 50%
Bacterial Special Interest Group. Final agreement was of individuals, is an increased or altered vaginal dis-
achieved by a majority decision following an open vote charge. In about a quarter of individuals, lower
in this meeting. The draft guideline was appraised with abdominal pain is present. Gonorrhoea rarely causes
the AGREE instrument, posted on the BASHH web- intermenstrual bleeding and menorrhagia. On exami-
site for a consultation period of two months and nation, a mucopurulent endocervical discharge may
assessed by a Health Advisor. be seen and easily induced endocervical bleeding may
be present. However, pelvic and lower abdominal ten-
derness is an uncommon examination finding in the
PATIENT AND PUBLIC INVOLVEMENT absence of coinfection with Chlamydia trachomatis.
A patient representative was a member of the writing
group, attended writing group meetings and was Rectal infection
involved in the development of the guideline. In addi-
Most cases are asymptomatic but symptoms may
tion, attendees for treatment of confirmed gonorrhoea
include anal discharge and perianal/anal pain or dis-
at a specialist sexual health service were consulted on
comfort. Rectal infection in cisgender women is present
treatment options (including epidemiological treat-
in up to a third of cases of urogenital infection, and
ment) and test of cure. individuals may not report a history of anal sex.
Limited evidence suggests that rectal infection in the
AETIOLOGY absence of urogenital infection is uncommon.4
Gonorrhoea is caused by the Gram-negative diplococ-
cus Neisseria gonorrhoeae. The primary sites of infec- Pharyngeal infection
tion are the columnar epithelium-lined mucous This is predominantly asymptomatic but is occasional-
membranes of the urethra, endocervix, rectum, phar- ly associated with a sore throat.
ynx and conjunctiva. Transmission is by direct inocu-
lation of infected secretions from one mucous Complicated infection
membrane to another. Secondary infection to other
Transluminal spread of N. gonorrhoeae from the ure-
anatomical sites, through systemic or transluminal
thra or endocervix may occur and cause epididymo-
spread, can also occur.
orchitis, prostatitis or pelvic inflammatory disease
(PID). Haematogenous dissemination may occur
CLINICAL FEATURES1–3 from infected mucous membranes to cause skin lesions,
Symptoms and signs of infection with gonorrhoea arthralgia, arthritis and tenosynovitis (disseminated
depend, in part, on the site of infection. Co-existing gonococcal infection). In a study involving nearly
infections and conditions such as Chlamydia trachoma- 4,000 cisgender women attending a sexual health
clinic in the UK, PID was reported in approximately
tis, Trichomonas vaginalis, Mycoplasma genitalium,
14% of those with gonorrhoea.5
Candida albicans and bacterial vaginosis, are not
uncommon and these should be considered as a possi-
ble cause for an individual’s symptoms. DIAGNOSIS AND SPECIMEN
COLLECTION
Penile urethral infection This section should be read in conjunction with Public
Symptoms occur in over 90% of individuals, with dis- Health England’s ‘Guidance for the detection of
charge and/or dysuria appearing two to five days fol- gonorrhoea in England 2014’.6 The diagnosis of
lowing exposure. A mucopurulent urethral discharge is gonorrhoea is established by the detection of
often present on examination. Rarely, individuals may N. gonorrhoeae at an infected site, either by nucleic
6 International Journal of STD & AIDS 31(1)

acid amplification tests (NAATs) or by culture. The be present at significant levels, particularly in the
approach and method used to test for gonorrhoea pharynx.18 It is recommended that laboratories con-
will be influenced by the clinical setting, storage and firm any reactive test with an alternative molecular
transport system to the laboratory, local prevalence target if the positive predictive value of the initial
of infection and the range of tests available in the lab- test for the population tested is less than 90%
oratory. No test for gonorrhoea offers 100% sensitivity (Grade 1B).6,7,19 This is particularly important for
and specificity.6–9 extra-genital specimens.
• Pooling of self-collected or clinician-collected rectal,
Microscopy pharyngeal and urine samples from the same indi-
vidual could provide cost savings. There is a small
• Microscopy of Gram-stained genital specimens evidence base with mixed results using different test-
allows direct visualisation of N. gonorrhoeae as ing platforms, specimen collection and pooling
monomorphic Gram-negative diplococci within methods. The largest study to date has shown that
polymorphonuclear leukocytes. pooling of self-taken swabs has lower sensitivity for
• Penile urethra detection of N. gonorrhoeae from pharyngeal sites,
䊊 Microscopy of urethral or meatal swab smears when compared with single site testing.20 Any ser-
has good sensitivity (90–95%) in people with dis- vice considering the implementation of pooling
charge from the penile urethra and is recom- should perform appropriate clinical evaluation.
mended to facilitate immediate presumptive • Penile urethra
diagnosis in these individuals (Grade 1C).1 䊊 NAATs show equivalent sensitivity in urine and
䊊 Microscopy of penile urethral smears in those urethral swab specimens from cisgender men
without symptoms is less sensitive (50–75%), although a first-pass urine is the preferred
therefore it is not recommended in asymptomatic sample.7,21
individuals (Grade 1C).1 • Female urethra and endocervix
• Female urethra and endocervix 䊊 Self-collected or clinician-collected vulvovaginal
䊊 Microscopy has only 37–50% and 20% sensitiv- swabs perform better than endocervical swabs
ity compared with culture for detecting gonor- and significantly better than urine for cisgender
rhoea from endocervical and female urethral women.6,7,9,22–24 Vulvovaginal swabs are there-
smears, respectively.3 fore recommended as the optimal specimen
䊊 The sensitivity of cervical microscopy compared (Grade 1A).
to NAATs in a more recent study was only 䊊 For people who have had a hysterectomy, there is
16%.10 no evidence on optimal sampling site. We suggest
䊊 Female urethral and cervical microscopy is there- considering urine and VVS for NAAT with sub-
fore not routinely recommended (Grade 1C). sequent culture from that site if positive
• Rectum and pharynx (Grade 2D).
䊊 Ano-rectal smears and microscopy should be • Rectum and pharynx
offered if rectal symptoms are present (Grade 䊊 Infection can occur at multiple sites and an indi-
1C).11 vidual can be infected with more than one strain
䊊 The sensitivity of microscopy for detecting of N. gonorrhoeae.25–27
asymptomatic rectal infection is low and is not 䊊 Rectal and pharyngeal sampling should be rou-
recommended (Grade 1C).12 tine in all men who have sex with men (MSM), as
䊊 Microscopy of pharyngeal specimens is not rec- recommended by the BASHH guideline on the
ommended (Grade 1C). sexual health care of MSM, considered in
women who are sexual contacts of gonorrhoea
and be guided by an assessment of risk and
Nucleic acid amplification tests symptoms in everyone else.28–30
䊊 Oropharyngeal infection is more difficult to
• NAATs are more sensitive than culture, particularly treat.31–34 Therefore, anyone with genital gonor-
for oropharyngeal and rectal sites.13–15 NAATs rhoea (regardless of gender or reported sexual
show high sensitivity (>95%) in both symptomatic behaviour) should have pharyngeal sampling if
and asymptomatic infection.14,16,17 Therefore, either of the following apply (Grade 1D):
although NAATs are not licensed for use at extra- i. Susceptibility results are not available and
genital sites, their use is recommended.6 the infection may have been acquired in the
• Commercially available NAATs differ in their cross- Asia-Pacific region. This is because of high
reactivity to commensal Neisseria species which may levels of antimicrobial resistance in that
Fifer et al. 7

region35–38 which may lead to treatment • Extragenital testing should be guided by sexual his-
failure tory and symptoms.
ii. Genital infection with a confirmed ceftriax-
one-resistant strain Testing for other STIs
Approximately 19% of patients with gonorrhoea have
concurrent C. trachomatis infection.43 Testing for other
Culture STIs should be undertaken according to BASHH STI
• The primary role of culture is for antimicrobial sus- testing guidelines.44
ceptibility testing, which is of increasing importance
as antimicrobial resistance in N. gonorrhoeae contin- Timing of testing
ues to evolve and spread. Infection cannot be ruled out in individuals who test
• Specimens for culture (urethral, endocervical, neo- within two weeks of sexual contact with an infected
vaginal, anorectal and pharyngeal swabs) should be partner. Therefore, it is recommended that patients
taken alongside NAATs from people suspected clin- return for repeat testing after this window period if
ically of having gonorrhoea, and from sexual epidemiological treatment is not given (Grade 1D).45
contacts.6
• All individuals with gonorrhoea diagnosed by
NAAT should have cultures taken for susceptibility MANAGEMENT
testing prior to treatment (Grade 1D).
General advice
• For culture, the sensitivity depends on several fac-
tors including time from sample collection to plat- Patients should be given a detailed explanation of their
ing. Services should seek to minimise this time condition with particular emphasis on the implications
whether by direct plating in the clinic or use of trans- for the health of themselves and their partner(s). This
port media with prompt transfer for plating in the should be reinforced, if necessary, with clear and accu-
laboratory. rate written information (Grade 1D). Patients should
be advised to abstain from sexual intercourse until
Considerations for people following genital seven days after they and their partner(s) have complet-
ed treatment (Grade 1D).
reconstructive surgery (GRS)
• The susceptibility of a site to gonococcal infection is Treatment
likely to be related to the nature of the reconstruc-
Indications for therapy:
tion, with sites constructed from mucosal tissue (e.g.
from the vaginal or bowel mucosa) being more sus-
1. Identification of intracellular Gram-negative diplo-
ceptible than sites constructed from skin.
cocci on microscopy
• Gonococcal infections of the urethra,39 sigmoid neo-
2. A positive culture for N. gonorrhoeae
vagina40 and penile skin-lined neovagina41,42 have 3. A confirmed positive NAAT for N. gonorrhoeae
all been reported following GRS. Gonococcal infec- 4. Sexual partner of confirmed case of gonococcal
tions of the neopenis are rare. infection (See section below on Sexual Partners)
• The sensitivity of microscopy for the diagnosis of
gonococcal infection of the neovagina and neopenis Treatment of uncomplicated ano-genital and pharyngeal
is not known. Examination of a Gram-stained smear infection in adults
from a bowel segment neovagina may facilitate a
presumptive diagnosis of gonorrhoea and could be When antimicrobial susceptibility is not known prior to
considered (Grade 1D). treatment:
• We recommend that optimal genital testing in trans- Ceftriaxone 1 g intramuscularly as a single dose
gender women at risk of gonorrhoea should include (Grade 1C)
swabs from the neovagina and first-pass urine When antimicrobial susceptibility is known prior to
(Grade 1D). treatment:
• We recommend first-pass urine as the specimen of Ciprofloxacin 500 mg orally as a single dose46,47 (Grade
choice from people with a neopenis (Grade 1D). 1A) (See caution in section “Use of ciprofloxacin first
Where the vagina is still present following GRS a line when infection is known to be susceptible”)
vaginal swab should be considered as directed by The prevalence of ciprofloxacin resistance in the UK
the sexual history and symptoms. is high (36.4% in 2017).43 Therefore, we only
8 International Journal of STD & AIDS 31(1)

recommend considering ciprofloxacin as first-line treat- • Since 2011 the prevalence of azithromycin resis-
ment if phenotypic or genotypic antimicrobial suscep- tance in the UK and globally has increased
tibility data indicates susceptibility to ciprofloxacin at (9.2% in GRASP 2017, 7.5% in Euro-GASP
all suspected sites of infection. Molecular testing for 2016).43,62–66 There has also been sustained
gyrA gene mutations of NAAT-positive gonorrhoea transmission of high-level azithromycin-resistant
samples is feasible to identify patients who could be N. gonorrhoeae across the UK67 and clusters
treated with ciprofloxacin27,48,49 although commercial reported elsewhere.68
tests are not currently available in the UK. • Although some of the internationally reported
ceftriaxone-resistant isolates are susceptible to
The move to ceftriaxone monotherapy represents a major azithromycin,51,52,55 a 1 g dose of azithromycin
change from the 2011 guideline. There is a lack of high may be insufficient to clear infection. In a ran-
quality evidence regarding the best strategy to delay the domized controlled trial (RCT), the combination
emergence of resistance. However, for the reasons out- of gentamicin 240 mg IM with azithromycin 1 g
lined below, monotherapy is recommended. A high only cleared infection in 91% of participants and
level of vigilance through use of culture, follow up of did not demonstrate non-inferiority compared to
patients and test of cure coupled with maintenance of ceftriaxone 500 mg IM with azithromycin 1 g.
strong surveillance is vital in order to monitor the This suggests a 1 g dose of azithromycin is insuf-
impact of this approach. ficient to treat gonorrhoea.69
• For infections with azithromycin MICs around
1. The dose of ceftriaxone has been increased from the breakpoint (>0.5 mg/L), a 2 g dose of azith-
500 mg to 1 g romycin could potentially be more effective than
• The prevalence of ceftriaxone resistance (MIC 1 g. However, the 2 g dose would not be effective
>0.125 mg/L) is very low in England and Wales, against high-level azithromycin-resistant isolates.
however, there has been an increase in the modal In addition, the incidence of gastrointestinal side-
ceftriaxone MIC distribution (i.e. an increase in effects is higher with 2 g azithromycin and so this
the proportion of isolates with reduced dose may not be acceptable to patients or
susceptibility).43,50 clinicians.70
• Ceftriaxone-resistant isolates have been identified • With higher doses of azithromycin, the duration
in the UK32,33 and globally.51–55 The UK cases, of sub-MIC levels at mucosal surfaces is extended
which were resistant to both ceftriaxone and for up to four weeks.71–73 If a patient is reinfected
azithromycin (including one case of high-level with gonorrhoea during this time period, this
azithromycin resistance, MIC 256 mg/L), had could potentially select for azithromycin
epidemiological links to the Asia-Pacific region resistance.
• Other reasons for avoiding azithromycin in the
where significant levels of reduced susceptibility
treatment of gonorrhoea centre around antibiotic
and resistance to ceftriaxone have been
stewardship in sexual health more generally, par-
reported.35,36
ticularly the fears of accelerating the induction
• Although a lower dose of ceftriaxone would be
and spread of resistance in other STIs such as
adequate to treat the majority of gonococcal
Mycoplasma genitalium and Treponema pallidum.
strains that are currently circulating in the UK, 3. Use of ciprofloxacin first line when infection is known
data suggest that ceftriaxone 1 g would be more to be susceptible
effective against most isolates with increased • Using alternative antibiotics where appropriate
MICs.56 can reduce the selective pressure which comes
• Therefore, in an attempt to ensure successful from the universal use of ceftriaxone and this
treatment of strains with reduced susceptibility, may delay the emergence of ceftriaxone
the recommended dose of ceftriaxone has been resistance.49,74
increased to 1 g. • The writing group are aware of the alert from the
2. Dual therapy with azithromycin 1 g is no longer European Medicines Agency (EMA) following
recommended their 2018 review of serious side effects associated
• Azithromycin 1 g was added to recommended with the use of quinolone and fluoroquinolone
therapy in 2011 in an attempt to ensure successful antibiotics.75 These include side effects involving
treatment of infection with reduced susceptibility muscles, tendons, joints and the nervous system.
to ceftriaxone.56 Evidence to suggest synergy Ciprofloxacin should be avoided in people who
between cephalosporins and azithromycin in have previously had serious side effects with a
vitro is inconclusive.57–61 fluoroquinolone or quinolone antibiotic. It
Fifer et al. 9

should be used with caution in those over the age • Spectinomycin 2 g intramuscularly as a single dose
of 60 years, those taking a corticosteroid, people plus azithromycin 2 g orally (Grade 1B)
with kidney disease and those who have had an 䊊 Spectinomycin is not recommended for pharyn-
organ transplantation. geal infection because of poor efficacy.31 In addi-
• Gonorrhoea is a serious infection and the potential tion, spectinomycin may be difficult to obtain as
benefit of using ciprofloxacin in people with sus- it is an unlicensed imported product.
ceptible infection will outweigh the potential risks. • Azithromycin 2 g as a single oral dose (Grade 1B)
䊊 The clinical efficacy of azithromycin does not
always correlate with in vitro susceptibility test-
Alternative regimens ing83 and azithromycin resistance is high.43
The following options have all been associated with
treatment failure when used as monotherapy particu- Treatment of complicated infections
larly when used for pharyngeal infection,76–79 therefore Gonococcal PID
it is recommended to use dual therapy with azithromy-
cin 2 g where possible (Grade 2C). Clinicians using • Ceftriaxone 1 g intramuscularly as a single dose in
alternative regimens for empirical treatment of gonor- addition to the regimen chosen to treat PID (see
rhoea without antibiotic susceptibility data are recom- BASHH PID guideline)
mended to regularly review local and national trends in
gonococcal antimicrobial resistance. Gonococcal epididymo-orchitis
Alternative regimens may be given because of aller-
gy, needle phobia or other absolute or relative contra- • Ceftriaxone 1 g intramuscularly as a single dose in
indications. In patients with penicillin allergy there is addition to the regimen chosen to treat epididymo-
ample evidence to allow the safe use of all but a few orchitis (see BASHH epididymo-orchitis guideline)
early generation cephalosporins (e.g. cephalexin, cefa-
Gonococcal conjunctivitis
clor and cefadroxil), and third-generation cephalospor-
ins such as cefixime and ceftriaxone show negligible
• Ceftriaxone 1 g intramuscularly as a single dose
cross-allergy with penicillins.80,81
(Grade 2D)
Therefore, in penicillin-allergic patients ceftriaxone
䊊 There is a single study of the treatment of gono-
and cefixime are suitable treatment options, unless there
coccal conjunctivitis conducted in twelve
is a history of severe hypersensitivity (e.g. anaphylactic
adults.84 All were successfully treated with a
reaction) to any beta-lactam antibacterial agent (penicil-
single dose of ceftriaxone.
lins, cephalosporins, monobactams and carbapenems).81
䊊 The eye should be irrigated with saline/water.
• Cefixime 400 mg orally as a single dose plus azith-
There is a lack of evidence to guide treatment options
romycin 2 g orally (Grade 1B)
if there is a history of penicillin anaphylaxis or estab-
䊊 Only advisable if an intramuscular injection is
lished cephalosporin allergy. Treatment should be based
contraindicated or refused by the patient.
on antimicrobial susceptibility results where available.
Resistance to cefixime is currently low in the
UK.43 Disseminated gonococcal infection
• Gentamicin 240 mg intramuscularly as a single dose
plus azithromycin 2 g orally (Grade 1A) • Ceftriaxone 1 g intramuscularly or intravenous every
䊊 A large, UK-based, RCT examined the efficacy 24 hours or
and safety of gentamicin for the treatment of • Cefotaxime 1 g intravenous every eight hours or
gonorrhoea.69 This study used gentamicin in • Ciprofloxacin 500 mg intravenous every 12 hours (if
combination with 1 g of azithromycin. the infection is known to be susceptible) or
Microbiological cure (negative NAAT two • Spectinomycin 2 g intramuscularly every 12 hours
weeks after treatment) was achieved in 94% of
urogenital, 90% of rectal and 80% of pharyngeal Therapy should continue for seven days but may be
infections. Another randomised trial used a 2 g switched 24–48 hours after symptoms improve to one
dose of azithromycin in combination with genta- of the following oral regimens guided by sensitivities:
micin.82 This found 100% clearance of infection,
however, few extragenital infections were includ- • Cefixime 400 mg twice daily or
ed and culture was used to confirm clearance (i.e. • Ciprofloxacin 500 mg twice daily or
it is likely to overestimate the effectiveness). • Ofloxacin 400 mg twice daily
10 International Journal of STD & AIDS 31(1)

Pregnancy and breastfeeding85–87 Treatment of contacts

Pregnant and breastfeeding individuals should not be Epidemiological treatment is not needed for all sexual
treated with quinolone or tetracycline antimicrobials. contacts, and ideally treatment should only be given to
Pregnancy does not diminish treatment efficacy. those partners who test positive for gonorrhoea.
However, an infection may be missed if a test is per-
• Ceftriaxone 1 g intramuscularly as a single dose formed too soon after a potential exposure. The time
(Grade 1A) or between exposure and a positive test result may vary
• Spectinomycin 2 g intramuscularly as a single dose depending on a number of host, pathogen and diagnos-
(Grade 1A) tic factors. There is a lack of evidence to support recom-
䊊 Spectinomycin is in the FDA pregnancy category mendations for the optimal time for testing. Therefore,
B and therefore not expected to be harmful and in order to reduce the unnecessary use of antibiotics, we
can be used if no suitable alternatives. It is not recommend the following as a pragmatic approach:
known if it is excreted in breastmilk and should
be used with caution in those who are • For those presenting after 14 days of exposure we
breastfeeding. recommend treatment only following a positive test
• Azithromycin 2 g as a single oral dose (Grade 1B) for gonorrhoea.90
䊊 The manufacturer of azithromycin advises use • For those presenting within 14 days of exposure we
only if adequate alternatives are not available. recommend considering epidemiological treatment
In addition, azithromycin should only be used based on a clinical risk assessment and following a
if isolate known to be susceptible. discussion with the patient. In asymptomatic indi-
viduals, it may be appropriate to not give epidemi-
ological treatment, and to repeat testing 2 weeks
HIV-positive individuals after exposure.
HIV-positive individuals with gonorrhoea should be
managed in the same way as HIV-negative individuals. FOLLOW-UP AND TEST OF CURE
(TOC)
Chlamydia coinfection All patients diagnosed with gonorrhoea should be
advised to return for TOC, with extra emphasis given
• Treatment for confirmed or suspected chlamydia
to patients:
coinfection should follow the current BASHH
guideline for the management of chlamydia. 1. With persistent symptoms or signs
• If an individual has already received azithromycin 2. With pharyngeal infection
2 g for the treatment of gonorrhoea then this 3. Treated with anything other than first line recom-
should be sufficient to treat chlamydia and no fur- mended regimen when antimicrobial susceptibility
ther doses of azithromycin are required. unknown
4. Who acquired infection in the Asia-Pacific region
when antimicrobial susceptibility unknown
SEXUAL PARTNERS
Assessment after treatment may be helpful to:
Partner notification
Partner notification should be pursued in all patients • detect treatment failure and emerging resistance
identified with gonococcal infection. Action and out- • confirm compliance with treatment
• ensure resolution of symptoms
comes should be documented.88
• enquire about adverse reactions
Partner notification should follow national recom-
• take a sexual history to explore the possibility of
mendations.89 The following partners should be notified:
reinfection
• pursue partner notification and health promotion
• All partners within the preceding two weeks (or the
last partner if longer than two weeks ago) of male
patients with symptomatic urethral infection; Method and timing of TOC
• All partners within the preceding three months of A positive TOC could be due to treatment failure, rein-
patients with infection at other sites or asymptom- fection or residual non-viable organism and should be
atic infection. interpreted in the clinical context.
Fifer et al. 11

• Culture, performed at least 72 hours after comple- QUALIFYING STATEMENT

tion of therapy, should be used if symptoms or signs
Decisions to follow these recommendations must be
are present at time of TOC.91
based on professional clinical judgement, consideration
• NAAT should be used if asymptomatic, followed by
of individual patient circumstances and available
culture if NAAT-positive.
resources.
• The time to a negative TOC using NAATs is vari-
All possible care has been undertaken to ensure spec-
able and there are limited data to inform optimum
ification of the correct dosage of medication and route
time to TOC. However, most individuals should be of administration. However, it remains the responsibil-
negative seven days following treatment where an ity of the prescribing clinician to ensure the accuracy
RNA NAAT is used and 14 days following treat- and appropriateness of the medication they prescribe.
ment when using a DNA NAAT.92
• We recommend TOC should be performed at an
Time scale for next revision
appropriate time depending on the type of NAAT
used (Grade 1B). An author group will be invited by the BASHH CEG
to review and revise the guideline in 2023 using the
BASHH framework for guideline development.
Treatment failures However, addenda may be issued sooner than 2023,
particularly if relevant new data are available relating
Cases of possible ceftriaxone treatment failure in to treatment or antimicrobial resistance.
England should be reported to Public Health England
using the on-line form: https://hivstiwebportal.phe.org. Acknowledgements
uk/login.aspx We thank the following for their valuable contributions to
Only authorised users are permitted to access this this guideline: Keith Radcliffe (Chair) and members of the
secure website. All specialist sexual health clinics BASHH Clinical Effectiveness Group; Professor Cathy Ison
should have access. If required, usernames and pass- (Chair), Dr Paddy Horner, Dr Michelle Cole and members of
words can be obtained from [email protected]. the BASHH Bacterial Special Interest Group; Professor
David Livermore (Chair), Dr Gwenda Hughes and
Professor Jonathan Ross on behalf of the GRASP steering
group; Dr Ann Sullivan (Chair), Dr Nisha Pal on behalf of
AUDITABLE OUTCOME MEASURES the BASHH National Audit Group; Dr Kate Nambiar on
behalf of the BASHH Gender & Sexual Minorities Special
• All individuals with gonorrhoea diagnosed by
Interest Group; Dr Richard Gilson (University College
NAAT should have cultures taken for susceptibility London); Dr Paul Lee (Medicines and Healthcare products
testing prior to treatment (performance standard Regulatory Agency); Jane Holder, clinical nurse specialist;
97%) patient representative and other patients who gave advice
• Individuals treated for gonorrhoea should have a during the development of this guideline; and those who
test of cure performed (performance standard 97%) made comments during the web based consultation: Jake
• Individuals diagnosed with gonorrhoea should be Bayley, Rachel Drayton, Anne Edwards, Emily James,
tested for all sexually transmitted infections includ- David Kellock, Neil Lazaro, Vincent Lee, Nigel O’Farrell,
ing HIV (unless previously diagnosed with HIV) Karin O’Sullivan, Cecilia Priestley, Jonathan Shaw, Jackie
Sherrard, Selena Singh, Harriet Wallace, Andrew Whyte,
(performance standard 97%)
Sathish Thomas William.
• Individuals diagnosed with gonorrhoea should have
partner notification carried out in accordance with
Declaration of conflicting interests
the BASHH statement on partner notification (per-
formance standard 97%) The authors declared the following potential conflicts of
• Individuals diagnosed with gonorrhoea should be interest with respect to the research, authorship, and/or pub-
offered information (written or digital) about their lication of this article: All authors have signed BASHH con-
diagnosis and management (performance standard flict of interest forms.
97%)
• Individuals diagnosed with gonorrhoea should Funding
receive first-line treatment or the reasons for not The authors received no financial support for the research,
doing so documented (performance standard 97%) authorship, and/or publication of this article.
• Cases of possible treatment failures with ceftriaxone
should be reported to Public Health England (per- ORCID iD
formance standard 97%) Helen Fifer https://orcid.org/0000-0001-7756-403X
12 International Journal of STD & AIDS 31(1)

References 14. Gaydos CA, Van Der Pol B, Jett-Goheen M, et al.

1. Sherrard J and Barlow D. Gonorrhoea in men: clinical Performance of the Cepheid CT/NG Xpert Rapid PCR
and diagnostic aspects. Genitourin Med 1996; 72(6): Test for Detection of Chlamydia trachomatis and
422–426. Neisseria gonorrhoeae. J Clin Microbiol 2013; 51(6):
2. Lewis DA, Bond M, Butt KD, et al. A one-year survey of 1666–1672. doi: 10.1128/JCM.03461-12.
gonococcal infection seen in the genitourinary medicine 15. Cornelisse VJ, Chow EP, Huffam S, et al. Increased
department of a London district general hospital. Int J Detection of Pharyngeal and Rectal Gonorrhea in Men
STD AIDS 1999; 10(9): 588–94. doi: 10.1258/ Who Have Sex With Men After Transition From Culture
0956462991914717. To Nucleic Acid Amplification Testing. Sex Transm Dis
3. Barlow D and Phillips I. Gonorrhoea in women. 2017; 44(2): 114–117. doi: 10.1097/OLQ.
Diagnostic, clinical, and laboratory aspects. Lancet 0000000000000553.
1978; 1(8067): 761–764. 16. Van Der Pol B, Hook EW, 3rd, Williams JA, et al.
4. Barry PM, Kent CK, Philip SS, et al. Results of a pro- Performance of the BD CTQx and GCQx Amplified
gram to test women for rectal chlamydia and gonorrhea. Assays on the BD Viper LT Compared With the BD
Obstet Gynecol 2010; 115(4): 753–759. doi: 10.1097/ Viper XTR System. Sex Transm Dis 2015; 42(9):
AOG.0b013e3181d444f6 [published Online First: 2010/ 521–523. doi: 10.1097/OLQ.0000000000000313.
03/24].. 17. Geelen TH, Rossen JW, Beerens AM, et al. Performance
5. Morris GC, Stewart CM, Schoeman SA, et al. A cross- of Cobas(R) 4800 and m2000 real-time assays for detec-
sectional study showing differences in the clinical diagno- tion of Chlamydia trachomatis and Neisseria gonor-
sis of pelvic inflammatory disease according to the expe- rhoeae in rectal and self-collected vaginal specimen.
rience of clinicians: implications for training and audit. Diagn Microbiol Infect Dis 2013; 77(2): 101–105. doi:
Sex Transm Infect 2014; 90(6): 445–451. doi: 10.1136/sex- 10.1016/j.diagmicrobio.2013.06.020.
trans-2014-051646. 18. Palmer HM, Mallinson H, Wood RL, et al. Evaluation of
6. Hughes G, Ison C, Field N, et al. Guidance for the detec- the specificities of five DNA amplification methods for
tion of gonorrhoea in England. In: Public Health the detection of Neisseria gonorrhoeae. J Clin Microbiol
England, ed. https://assets.publishing.service.gov.uk/gov 2003; 41(2): 835–837.
ernment/uploads/system/uploads/attachment_data/file/ 19. Pope CF, Hay P, Alexander S, et al. Positive predictive
40 5293/170215_Gonorrhoea_testing_guidance_ value of the Becton Dickinson VIPER system and the
REVISED 2_.pdf, 2014. ProbeTec GC Q x assay, in extracted mode, for detection
7. Whiley DM, Garland SM, Harnett G, et al. Exploring of Neisseria gonorrhoeae. Sex Transm Infect 2010; 86(6):
’best practice’ for nucleic acid detection of Neisseria gon- 465–469. doi: 10.1136/sti.2010.044065.
orrhoeae. Sex Health 2008; 5(1): 17–23. 20. Sultan B, White JA, Fish R, et al. The “3 in 1” Study:
8. Van Dyck E, Ieven M, Pattyn S, et al. Detection of
Pooling Self-Taken Pharyngeal, Urethral, and Rectal
Chlamydia trachomatis and Neisseria gonorrhoeae by
Samples into a Single Sample for Analysis for
enzyme immunoassay, culture, and three nucleic acid
Detection of Neisseria gonorrhoeae and Chlamydia tra-
amplification tests. J Clin Microbiol 2001; 39(5):
chomatis in Men Who Have Sex with Men. J Clin
1751–1756. doi: 10.1128/JCM.39.5.1751-1756.2001.
Microbiol 2016; 54(3): 650–656. doi: 10.1128/
9. Cook RL, Hutchison SL, Ostergaard L, et al. Systematic
JCM.02460-15.
review: noninvasive testing for Chlamydia trachomatis
21. Chernesky MA, Martin DH, Hook EW, et al. Ability of
and Neisseria gonorrhoeae. Ann Intern Med 2005;
new APTIMA CT and APTIMA GC assays to detect
142(11): 914–925.
10. Thorley N and Radcliffe K. The performance and clinical Chlamydia trachomatis and Neisseria gonorrhoeae in
utility of cervical microscopy for the diagnosis of gonor- male urine and urethral swabs. J Clin Microbiol 2005;
rhoea in women in the era of the NAAT. Int J STD AIDS 43(1): 127–131. doi: 10.1128/JCM.43.1.127-131.2005.
2015; 26(9): 656–660. doi: 10.1177/0956462414551233. 22. Schachter J, Chernesky MA, Willis DE, et al. Vaginal
11. Grover D, Prime KP, Prince MV, et al. Rectal gonor- swabs are the specimens of choice when screening for
rhoea in men – is microscopy still a useful tool? Chlamydia trachomatis and Neisseria gonorrhoeae: results
International Journal of STD & AIDS 2006; 17(4): from a multicenter evaluation of the APTIMA assays for
277–279. doi: 10.1258/095646206776253363. both infections. Sex Transm Dis 2005; 32(12): 725–728.
12. Forni J, Miles K and Hamill M. Microscopy detection of 23. Stewart CM, Schoeman SA, Booth RA, et al. Assessment
rectal gonorrhoea in asymptomatic men. International of self taken swabs versus clinician taken swab cultures
journal of STD & AIDS 2009; 20(11): 797–798. doi: for diagnosing gonorrhoea in women: single centre, diag-
10.1258/ijsa.2009.009186. nostic accuracy study. BMJ 2012; 345: e8107. doi:
13. Levy V, Blackmore CS and Klausner JD. Self-collection 10.1136/bmj.e8107.
of specimens for nucleic acid-based diagnosis of pharyn- 24. Van Der Pol B, Taylor SN, Liesenfeld O, et al. Vaginal
geal, cervicovaginal, urethral, and rectal Neisseria gonor- swabs are the optimal specimen for detection of genital
rhoeae and Chlamydia trachomatis infections. Methods Chlamydia trachomatis or Neisseria gonorrhoeae using
Mol Biol 2012; 903: 407–418. doi: 10.1007/978-1-61779- the Cobas 4800 CT/NG test. Sex Transm Dis 2013; 40(3):
937-2_28. 247–250. doi: 10.1097/OLQ.0b013e3182717833.
Fifer et al. 13

25. Benn PD, Rooney G, Carder C, et al. Chlamydia tracho- 38. Jiang FX, Lan Q, Le WJ, et al. Antimicrobial suscepti-
matis and Neisseria gonorrhoeae infection and the sexual bility of Neisseria gonorrhoeae isolates from Hefei
behaviour of men who have sex with men. Sex Transm (2014–2015): genetic characteristics of antimicrobial
Infect 2007; 83(2): 106–112. doi: 10.1136/sti.2006.021329. resistance. BMC Infect Dis 2017; 17(1): 366. doi:
26. Lavelle SJ, Jones KE, Mallinson H, et al. Finding, con- 10.1186/s12879-017-2472-z.
firming, and managing gonorrhoea in a population 39. Fiumara NJ and Asvadi S. Asymptomatic gonococcal
screened for chlamydia using the Gen-Probe Aptima urethritis in a male transsexual female. Br J Vener Dis
Combo2 assay. Sex Transm Infect 2006; 82(3): 221–224. 1978; 54(2): 130–131.
doi: 10.1136/sti.2005.017616. 40. van der Sluis WB, Bouman MB, Gijs L, et al.
27. Pond MJ, Hall CL, Miari VF, et al. Accurate detection of Gonorrhoea of the sigmoid neovagina in a male-to-
Neisseria gonorrhoeae ciprofloxacin susceptibility direct- female transgender. Int J STD AIDS 2015; 26(8):
ly from genital and extragenital clinical samples: towards 595–598. doi: 10.1177/0956462414544725.
genotype-guided antimicrobial therapy. J Antimicrob 41. Bodsworth NJ, Price R and Davies SC. Gonococcal
Chemother 2016; 71(4): 897–902. doi: 10.1093/jac/dkv432. infection of the neovagina in a male-to-female transsex-
28. van Liere G, Dukers-Muijrers N, Levels L, et al. High ual. Sex Transm Dis 1994; 21(4): 211–212.
Proportion of Anorectal Chlamydia trachomatis and 42. Haustein UF. [Pruritus of the artificial vagina of a trans-
Neisseria gonorrhoeae After Routine Universal sexual patient caused by gonococcal infection]. Hautarzt
Urogenital and Anorectal Screening in Women Visiting 1995; 46(12): 858–859.
the Sexually Transmitted Infection Clinic. Clin Infect Dis 43. Public Health England. Key findings from the
2017; 64(12): 1705–1710. doi: 10.1093/cid/cix243. Gonococcal Resistance to Antimicrobials Surveillance
29. Jin F, Prestage GP, Kippax SC, et al. Risk factors Programme (GRASP) 2017. 2018.
for genital and anal warts in a prospective cohort 44. BASHH Clinical Effectiveness Group. BASHH CEG
of HIV-negative homosexual men: the HIM study. guidance on tests for Sexually Transmitted Infections.
Sex Transm Dis 2007; 34(7): 488–493. doi: 10.1097/01. https://www.bashhguidelines.org/media/1084/sti-testing-
olq.0000245960.52668.e5. tables-2015-dec-update-4.pdf, 2015.
30. van Liere GA, Hoebe CJ, Niekamp AM, et al. Standard 45. FitzGerald M and Bedford C. National standards for the
symptom- and sexual history-based testing misses anorec- management of gonorrhoea. Int J STD AIDS 1996; 7(4):
tal Chlamydia trachomatis and Neisseria gonorrhoeae 298–300. doi: 10.1258/0956462961917861.
infections in swingers and men who have sex with men. 46. Echols RM, Heyd A, O’Keeffe BJ, et al. Single-dose cipro-
Sex Transm Dis 2013; 40(4): 285–289. doi: 10.1097/ floxacin for the treatment of uncomplicated gonorrhea: a
OLQ.0b013e31828098f8 [published Online First: 2013/ worldwide summary. Sex Transm Dis 1994; 21(6): 345–352.
03/15]. 47. Moran JS. Ciprofloxacin for gonorrhea–250 mg or 500
31. Moran JS and Levine WC. Drugs of choice for the treat- mg? Sex Transm Dis 1996; 23(2): 165–167.
ment of uncomplicated gonococcal infections. Clin Infect 48. Allan-Blitz LT, Wang X and Klausner JD. Wild-Type
Dis 1995; 20(Suppl 1): S47–S65. Gyrase A Genotype of Neisseria gonorrhoeae Predicts
32. Eyre DW, Sanderson ND, Lord E, et al. Gonorrhoea In Vitro Susceptibility to Ciprofloxacin: A Systematic
treatment failure caused by a Neisseria gonorrhoeae Review of the Literature and Meta-Analysis. Sex
strain with combined ceftriaxone and high-level Transm Dis 2017; 44(5): 261–265. doi: 10.1097/
azithromycin resistance, England, February 2018. OLQ.0000000000000591.
Euro Surveill 2018; 23(27). doi: 10.2807/1560-7917. 49. Allan-Blitz LT, Humphries RM, Hemarajata P, et al.
ES.2018.23.27.1800323. Implementation of a Rapid Genotypic Assay to
33. Fifer H, Natarajan U, Jones L, et al. Failure of Dual Promote Targeted Ciprofloxacin Therapy of Neisseria
Antimicrobial Therapy in Treatment of Gonorrhea. gonorrhoeae in a Large Health System. Clin Infect Dis
N Engl J Med 2016; 374(25): 2504–2506. doi: 10.1056/ 2017; 64(9): 1268–1270. doi: 10.1093/cid/ciw864 [pub-
NEJMc1512757. lished Online First: 2016/12/31].
34. Moran JS. Treating uncomplicated Neisseria gonor- 50. Town K, Obi C, Quaye N, et al. Drifting towards ceftri-
rhoeae infections: is the anatomic site of infection impor- axone treatment failure in gonorrhoea: risk factor analy-
tant? Sex Transm Dis 1995; 22(1): 39–47. sis of data from the Gonococcal Resistance to
35. Chen SC, Yin YP, Dai XQ, et al. First nationwide study Antimicrobials Surveillance Programme in England and
regarding ceftriaxone resistance and molecular epidemi- Wales. Sex Transm Infect 2017; 93(1): 39–45. doi:
ology of Neisseria gonorrhoeae in China. J Antimicrob 10.1136/sextrans-2016-052583.
Chemother 2016; 71(1): 92–99. doi: 10.1093/jac/dkv321. 51. Lefebvre B, Martin I, Demczuk W, et al. Ceftriaxone-
36. Peng T, Lin H, Liu Q, et al. Ceftriaxone susceptibility Resistant Neisseria gonorrhoeae, Canada, 2017. Emerg
and molecular characteristics of Neisseria gonorrhoeae Infect Dis 2018; 24(2) doi: 10.3201/eid2402.171756.
isolates in Changsha, China. J Infect Chemother 2017; 52. Camara J, Serra J, Ayats J, et al. Molecular characteri-
23(6): 385–389. doi: 10.1016/j.jiac.2017.03.007. zation of two high-level ceftriaxone-resistant Neisseria
37. Chen Y, Gong Y, Yang T, et al. Antimicrobial resistance gonorrhoeae isolates detected in Catalonia, Spain.
in Neisseria gonorrhoeae in China: a meta-analysis. BMC J Antimicrob Chemother 2012; 67(8): 1858–1860. doi:
Infect Dis 2016; 16: 108. doi: 10.1186/s12879-016-1435-0. 10.1093/jac/dks162.
14 International Journal of STD & AIDS 31(1)

53. Unemo M, Golparian D, Nicholas R, et al. High-level 65. Lahra MM, Ward A, Trembizki E, et al. Treatment
cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae guidelines after an outbreak of azithromycin-resistant
in France: novel penA mosaic allele in a successful inter- Neisseria gonorrhoeae in South Australia. Lancet Infect
national clone causes treatment failure. Antimicrob Dis 2017; 17(2): 133–134. doi: 10.1016/S1473-3099(17)
Agents Chemother 2012; 56(3): 1273–1280. doi: 10.1128/ 30007-5.
AAC.05760-11. 66. Wind CM, Schim van der Loeff MF, van Dam AP, et al.
54. Whiley DM, Jennison A, Pearson J, et al. Genetic char- Trends in antimicrobial susceptibility for azithromycin
acterisation of Neisseria gonorrhoeae resistant to both and ceftriaxone in Neisseria gonorrhoeae isolates in
ceftriaxone and azithromycin. Lancet Infect Dis 2018; Amsterdam, the Netherlands, between 2012 and 2015.
18(7): 717–718. doi: 10.1016/S1473-3099(18)30340-2. Euro Surveill 2017; 22(1). doi: 10.2807/1560-7917.
55. Lahra MM, Martin I, Demczuk W, et al. Cooperative ES.2017.22.1.30431.
Recognition of Internationally Disseminated 67. Fifer H, Cole M, Hughes G, et al. Sustained transmission
Ceftriaxone- Resistant Neisseria gonorrhoeae Strain. of high-level azithromycin-resistant Neisseria gonor-
Emerg Infect Dis 2018; 24(4). doi: 10.3201/ rhoeae in England: an observational study. Lancet
eid2404.171873. Infect Dis 2018; 18(5): 573–581. doi: 10.1016/S1473-
56. Chisholm SA, Mouton JW, Lewis DA, et al. 3099(18)30122-1.
Cephalosporin MIC creep among gonococci: time for a 68. Katz AR, Komeya AY, Kirkcaldy RD, et al. Cluster of
pharmacodynamic rethink? J Antimicrob Chemother Neisseria gonorrhoeae Isolates With High-level
2010; 65(10): 2141–2148. doi: 10.1093/jac/dkq289. Azithromycin Resistance and Decreased Ceftriaxone
57. Barbee LA, Soge OO, Holmes KK, et al. In vitro synergy Susceptibility, Hawaii, 2016. Clin Infect Dis 2017; 65(6):
testing of novel antimicrobial combination therapies 918–923. doi: 10.1093/cid/cix485.
against Neisseria gonorrhoeae. J Antimicrob Chemother 69. Ross JD, Harding J, Duley L, et al. LB1.5 The efficacy
2014; 69(6): 1572–1578. doi: 10.1093/jac/dkt540. and safety of gentamicin for the treatment of genital,
58. Pereira R, Cole MJ and Ison CA. Combination therapy pharyngeal and rectal gonorrhoea: a randomised con-
for gonorrhoea: in vitro synergy testing. J Antimicrob trolled trial. Sexually Transmitted Infections 2017;
93(Suppl 2): A42–A43. doi: 10.1136/sextrans-2017-
Chemother 2013; 68(3): 640–643. doi: 10.1093/jac/dks449.
59. Wind CM, de Vries HJ and van Dam AP. Determination 053264.106.
70. Handsfield HH, Dalu ZA, Martin DH, et al. Multicenter
of in vitro synergy for dual antimicrobial therapy against
trial of single-dose azithromycin vs. ceftriaxone in the
resistant Neisseria gonorrhoeae using Etest and agar dilu-
treatment of uncomplicated gonorrhea. Azithromycin
tion. Int J Antimicrob Agents 2015; 45(3): 305–308. doi:
Gonorrhea Study Group. Sex Transm Dis 1994; 21(2):
10.1016/j.ijantimicag.2014.10.020.
107–111.
60. Furuya R, Nakayama H, Kanayama A, et al. In vitro
71. Zheng S, Matzneller P, Zeitlinger M, et al. Development
synergistic effects of double combinations of beta-
of a population pharmacokinetic model
lactams and azithromycin against clinical isolates of
characterizing the tissue distribution of azithromycin in
Neisseria gonorrhoeae. J Infect Chemother 2006; 12(4):
healthy subjects. Antimicrob Agents Chemother 2014;
172–176. doi: 10.1007/s10156-006-0445-z.
58(11): 6675–6684. doi: 10.1128/AAC.02904-14.
61. Singh V, Bala M, Bhargava A, et al. In vitro efficacy of
72. Matzneller P, Krasniqi S, Kinzig M, et al. Blood, tissue,
21 dual antimicrobial combinations comprising novel and intracellular concentrations of azithromycin during
and currently recommended combinations for treatment and after end of therapy. Antimicrob Agents Chemother
of drug resistant gonorrhoea in future era. PLoS One 2013; 57(4): 1736–1742. doi: 10.1128/AAC.02011-12.
2018; 13(3): e0193678. doi: 10.1371/journal. 73. Crokaert F, Hubloux A and Cauchie P. A Phase I
pone.0193678. Determination of Azithromycin in Plasma during a
62. Cole MJ, Spiteri G, Jacobsson S, et al. Overall Low 6-Week Period in Normal Volunteers after a Standard
Extended-Spectrum Cephalosporin Resistance but high Dose of 500 mg Once Daily for 3 Days. Clin Drug
Azithromycin Resistance in Neisseria gonorrhoeae in 24 Investig 1998; 16(2): 161–166.
European Countries, 2015. BMC Infect Dis 2017; 17(1): 74. Buono SA, Watson TD, Borenstein LA, et al. Stemming
617. doi: 10.1186/s12879-017-2707-z. the tide of drug-resistant Neisseria gonorrhoeae: the need
63. Yasuda M, Ito S, Hatazaki K, et al. Remarkable increase for an individualized approach to treatment.
of Neisseria gonorrhoeae with decreased susceptibility of J Antimicrob Chemother 2015; 70(2): 374–381. doi:
azithromycin and increase in the failure of azithromycin 10.1093/jac/dku396 [published Online First: 2014/10/22].
therapy in male gonococcal urethritis in Sendai in 2015. 75. European Medicines Agency. Review of Quinolone- and
J Infect Chemother 2016; 22(12): 841–843. doi: 10.1016/j. fluoroquinolone- containing medicinal products. https://
jiac.2016.07.012. www.ema.europa.eu/en/medicines/human/referrals/quin
64. Wi T, Lahra MM, Ndowa F, et al. Antimicrobial resis- olone-fluoroquinolone-containing-medicinal-prod
tance in Neisseria gonorrhoeae: Global surveillance and a ucts2018 [accessed 10th January 2019].
call for international collaborative action. PLoS Med 76. Sathia L, Ellis B, Phillip S, et al. Pharyngeal gonorrhoea -
2017; 14(7): e1002344. doi: 10.1371/journal. is dual therapy the way forward? Int J STD AIDS 2007;
pmed.1002344. 18(9): 647–648. doi: 10.1258/095646207781568556.
Fifer et al. 15

77. Barbee LA, Kerani RP, Dombrowski JC, et al. A retro- 85. Brocklehurst P. Antibiotics for gonorrhoea in pregnancy.
spective comparative study of 2-drug oral and intramus- Cochrane Database Syst Rev 2002; (2): CD000098. doi:
cular cephalosporin treatment regimens for pharyngeal 10.1002/14651858.CD000098.
gonorrhea. Clin Infect Dis 2013; 56(11): 1539–1545. doi: 86. Cavenee MR, Farris JR, Spalding TR, et al. Treatment of
10.1093/cid/cit084. gonorrhea in pregnancy. Obstet Gynecol 1993; 81(1):
78. Ison CA, Hussey J, Sankar KN, et al. Gonorrhoea treat- 33–38.
ment failures to cefixime and azithromycin in England, 87. Ramus RM, Sheffield JS, Mayfield JA, et al. A random-
2010. Euro Surveill 2011; 16(14). ized trial that compared oral cefixime and intramuscular
79. Unemo M, Golparian D, Syversen G, et al. Two cases of ceftriaxone for the treatment of gonorrhea in pregnancy.
verified clinical failures using internationally recom- Am J Obstet Gynecol 2001; 185(3): 629–632. doi: 10.1067/
mended first-line cefixime for gonorrhoea treatment, mob.2001.117662.
Norway, 2010. Euro Surveill 2010; 15(47). 88. FitzGerald M, Thirlby D, Bell G, et al. National stand-
80. Pichichero ME and Casey JR. Safe use of selected ceph- ards for contact tracing in gonorrhoea. Royal College of
alosporins in penicillin-allergic patients: a meta-analysis.
Physicians, National Audit Development Programme in
Otolaryngol Head Neck Surg 2007; 136(3): 340–347. doi:
Sexual Health. Int J STD AIDS 1996; 7(4): 301. doi:
10.1016/j.otohns.2006.10.007.
10.1258/0956462961917870.
81. Zagursky RJ and Pichichero ME. Cross-reactivity in
89. McClean H, Radcliffe K, Sullivan A, et al. 2012 BASHH
beta-Lactam Allergy. The journal of allergy and clinical
statement on partner notification for sexually transmissi-
immunology In practice 2018; 6(1): 72–81.e1. doi: 10.1016/
ble infections. International Journal of STD & AIDS
j.jaip.2017.08.027 [published Online First: 2017/10/12].
82. Kirkcaldy RD, Weinstock HS, Moore PC, et al. The effi- 2013; 24(4): 253–261. doi: 10.1177/0956462412472804.
cacy and safety of gentamicin plus azithromycin and 90. Mensforth S and Radcliffe K. Is it time to reconsider
gemifloxacin plus azithromycin as treatment of uncom- epidemiological treatment for gonorrhoea? Int J STD
plicated gonorrhea. Clin Infect Dis 2014; 59(8): AIDS 2018; 29(10): 1043–1044. doi: 10.1177/
1083–1091. doi: 10.1093/cid/ciu521. 0956462418787611.
83. Tapsall JW, Shultz TR, Limnios EA, et al. Failure of 91. Jephcott AE. Microbiological diagnosis of gonorrhoea.
Azithromycin Therapy in Gonorrhea and Genitourin Med 1997; 73(4): 245–252.
Discorrelation With Laboratory Test Parameters. 92. Wind CM, Schim van der Loeff MF, Unemo M, et al.
Sexually Transmitted Diseases 1998; 25(10): 505–508. Test of Cure for Anogenital Gonorrhoea Using Modern
84. Haimovici R and Roussel TJ. Treatment of gonococcal RNA- Based and DNA-Based Nucleic Acid
conjunctivitis with single-dose intramuscular ceftriaxone. Amplification Tests: A Prospective Cohort Study. Clin
American journal of ophthalmology 1989; 107(5): 511–514. Infect Dis 2016; 262(11): 1348–1355. doi: 10.1093/cid/
[published Online First: 1989/05/15]. ciw141.